Digestive Tumors Research Articles

Tumor-related fungi and crosstalk with gut fungi in the tumor microenvironment.

Most studies on the human gut microbiome have focused on the bacterial fraction rather than fungal biomics, which as resulted in an incomplete understanding of the fungal microbiome. Recent advances in microbiota detection and next-generation sequencing technology have boosted an increase in research on fungi. Symbiotic fungi have become increasingly influential in health and disease and modulate various physiologic functions within the host. Fungal infections can result in high morbidity and mortality rates and are life-threatening in some immunocompromised patients. In addition to bacterial dysbiosis, alterations in fungal communities are important and have been linked to many diseases, including asthma, mental illness, and various cancers. When investigating cancer it is imperative to consider the role of fungi alongside viruses and bacteria. This review examined the impact of intestinal fungi and peri-tumor fungi on tumorigenesis, cancer progression, and response to anticancer therapies. The review highlights the specific involvement of some fungal species in cancers include digestive tract tumors such as colorectal, pancreatic, liver, and gastric cancers, as well as non-digestive tract tumors such as lung, melanoma, breast, and ovarian cancers. Furthermore, fungal mechanisms of action, including fungus-host recognition and immune regulation, biofilm formation, toxin and metabolite production in the tumor microenvironment, and the complex effects of fungus-bacteria interactions on tumorigenesis and development, highlight the significance of potential biomarkers in cancer diagnosis and treatment.

Advances in the diagnosis and treatment of MET-variant digestive tract tumors.

The receptor tyrosine kinase encoded by the MET gene plays an important role in various cellular processes such as growth, survival, migration and angiogenesis, and its abnormal activation is closely related to the occurrence and development of various tumors. This article reviews the recent advances in diagnosis and treatment of MET-variant digestive tract tumors. In terms of diagnosis, the application of next-generation sequencing technology and liquid biopsy technology makes the detection of MET variants more accurate and efficient, providing a reliable basis for individualized treatment. In terms of treatment, MET inhibitors such as crizotinib and cabotinib have shown good efficacy in clinical trials. In addition, the combination of immunotherapy and MET inhibitors also demonstrated potential synergies, further improving the therapeutic effect. However, the complexity and heterogeneity of drug resistance mechanisms are still one of the difficulties in current research. In the future, it is necessary to further deepen the understanding of the mechanism of MET variation and explore new combination treatment strategies to improve the overall survival rate and quality of life of patients. The diagnosis and treatment of MET-variant digestive tract tumors are moving towards precision and individualization, and have broad application prospects.

Integrin α2 in the microenvironment and the tumor compartment of digestive (gastrointestinal) cancers: emerging regulators and therapeutic opportunities.

Integrins are a family of cell surface membrane receptors and play a crucial role in facilitating bidirectional cell signaling. Integrin α2 (ITGA2) is expressed across a range of cell types, including epithelial cells, platelets, megakaryocytes, and fibroblasts, where it functions as a surface marker and it is implicated in the cell movements. The most recent findings have indicated that ITAG2 has the potential to function as a novel regulatory factor in cancer, responsible for driving tumorigenesis, inducing chemoresistance, regulating genomic instability and remodeling tumor microenvironment. Hence, we primarily focus on elucidating the biological function and mechanism of ITGA2 within the digestive tumor microenvironment, while highlighting its prospective utilization as a therapeutic target for cancer therapy.

Gram-negative microflora dysbiosis facilitates tumor progression and immune evasion by activating CCL3/CCL5-CCR1-MAPK-PD-L1 pathway in esophageal squamous cell carcinoma.

Gram-negative micro-flora dysbiosis occurs in multiple digestive tumors and is found to be the dominant micro-flora in esophageal squamous cell carcinoma (ESCC) micro-environment. The continuous stimulation of G- bacterium metabolites may cause tumorigenesis and reshape the micro-immune environment in ESCC. However, the mechanism of G- bacilli causing immune evasion in ESCC remains underexplored. We identified CC Chemokine receptor 1 (CCR1) as a tumor-indicating gene in ESCC. Interestingly, expression levels of CCR1 and PD-L1 were mutually up regulated after G- bacilli metabolites lipopolysaccharide (LPS) stimulation. Firstly, we found CCR1 high expression level to be associated with poor overall survival in ESCC. Importantly, we found that high level expression of CCR1 up-regulated PD-L1 expression by activating MAPK phosphorylation in ESCC and induced tumor malignant behavior. Finally, we found that T cells exhaustion and cytotoxicity suppression were associated with CCR1 expression in ESCC, which were decreased after CCR1 inhibiting. Our work identifies CCR1 as a potential immune check point regulator of PD-L1 and may cause T cell exhaustion and cytotoxicity suppression in ESCC micro-environment and highlights the potential value of CCR1 as therapeutic target of immunotherapy. Implications: The esophageal microbial environment and its metabolites significantly affect the outcome of immunotherapy for ESCC.

Clinical and cytological characteristics of malignant pericardial effusion and estimation of the rate of progression until its evacuation by pericardiocentesis

Abstract Introduction Pericardial effusion (PE) is a complication of neoplastic processes that worsens the prognosis and can lead to symptomatic presentations requiring pericardiocentesis (PC). There is limited literature regarding the evolution of PE from its onset to the need for PC, characteristics of these patients, progression rate of PE, and potential accelerating factors. Purpose This study aims to: i) Analyze the baseline characteristics of patients undergoing PC; ii) Evaluate the correlation between PE appearance and cytology; iii) Analyze the progression rate until PC performance. Methods This retrospective observational study includes patients with active neoplasia and significant symptomatic PE treated with PC at our hospital from 01/01/2010 to 06/30/23, with subsequent follow-up until 10/31/23. Clinical characteristics related to neoplastic processes and PE diagnosis were analyzed, including PE appearance, cytology, and computed tomography scans performed as neoplasia follow-up prior to PC. Results A total of 75 patients were included, with 6 excluded because of non-malignant conditions (2 acute pericarditis-related PE, 3 purulent PE, and 1 chylous PE). The remaining 69 patients had a median age of 59 years, with 55.1% being male. Lung neoplasm was most frequent (63.8%, with 84% adenocarcinoma), followed by lymphomas/lymphoid leukemia (7.3%), upper digestive tract (7.3%), and breast cancer (7.3%). 52.2% of PEs undergoing PC were diagnosed simultaneously with neoplasm (70.45% associated with pulmonary neoplasms); 43.5% had ECOG 1, and 89.9% had metastases (excluding PE) at PC. Cardiac tamponade was present in 27.5%, with percutaneous pericardiostomy added in 21.7%. PE appearance was sero-haematic in 49.3%, haematic in 36.2%, and serous in 14.5%. Cytology showed mostly positive results (69.2%: 50% in serous PE and 71.93% in haematic/sero-haematic PE). The median time from the last CT scan prior to PE to PC was 5 months (160 days, range: 24-943 days). PC recurrence was observed in 30.4% of cases. Follow-up mortality was 82.6%, higher in breast, renal, digestive, thymoma, and genital neoplasms (100%), with hematological neoplasms having the lowest mortality (40%), followed by pulmonary neoplasms (79.5%). Mortality was higher in patients with more lines of treatment at PC and with a higher number of metastases. The median time from PC to death was 2 months (68.5 days, range: 1 day-2007 days). Conclusions The most common neoplastic PE was associated with lung adenocarcinoma, though a variety of neoplasms were observed. Half of PEs were diagnosed concurrently with neoplasm diagnosis. Cytology sensitivity was not high, and PE appearance did not adequately predict outcomes. The median time from the last CT scan prior to PE to PC was 5 months, potentially guiding echocardiographic follow-up once PE is observed on CT. Overall mortality was high (82.6%), except for onco-hematological PE.Iconographic summary of malignant PE

Chronic exposure to hexavalent chromium induces esophageal tumorigenesis via activating the Notch signaling pathway.

Hexavalent chromium Cr(VI), as a well-established carcinogen, contributes to tumorigenesis for many human cancers, especially respiratory and digestive tumors. However, the potential function and relevant mechanism of Cr(VI) on the initiation of esophageal carcinogenesis are largely unknown. Here, immortalized human esophageal epithelial cells (HEECs) were induced to be malignantly transformed cells, termed HEEC-Cr(VI) cells, via chronic exposure to Cr(VI), which simulates the progress of esophageal tumorigenesis. In vitro and in vivo experiments demonstrated that HEEC-Cr(VI) cells obtain the ability of anchorage-independent growth, greater proliferative capacity, cancer stem cell properties, and the capacity to form subcutaneous xenografts in BALB/c nude mice when compared to their parental cells, HEECs. Additionally, HEEC-Cr(VI) cells exhibited weakened cell motility and enhanced cell adhesion. Interestingly, HEECs with acute exposure to Cr(VI) failed to display those malignant phenotypes of HEEC-Cr(VI) cells, suggesting that Cr(VI)‍-induced malignant transformation, but not Cr(VI) itself, is the cause for the tumor characteristics of HEEC-Cr(VI) cells. Mechanistically, chronic exposure to Cr(VI) induced abnormal activation of Notch signaling, which is crucial to maintaining the capacity for malignant proliferation and stemness of HEEC-Cr(VI) cells. As expected, N-‍[N-‍(3,5-difluorophenacetyl)‍-L-alanyl]‍-S-phenylglycine t-butyl ester (DAPT), an inhibitor for the Notch pathway, drastically attenuated cancerous phenotypes of HEEC-Cr(VI) cells. In conclusion, our study clarified the molecular mechanism underlying Cr(VI)‍-induced esophageal tumorigenesis, which provides novel insights for further basic research and clinical therapeutic strategies about Cr(VI)‍-associated esophageal cancer.

Hypoxia-Associated GPNMB+ Macrophages Promote Malignant Progression of Colorectal Cancer and Its RelatedRisk Signature Are Powerful Predictive Tool for theTreatment of Colorectal Cancer Patients.

Colorectal cancer (CRC) is a highly malignant tumor with hypoxia being a crucial feature during its progression. This study utilized multiple independent CRC cohorts for bioinformatics analysis and in vitro experiments to investigate the role of hypoxia-related subgroups in CRC. Machine learning was employed to construct risk features associated with this subgroup and further explore its therapeutic value in CRC. The study identified the GPNMB+ Macrophage (GPNMB+ Macr) subgroup as most relevant to hypoxia. GPNMB+ Macr showed significantly higher infiltration in tumor tissues compared to non-tumor tissues, increasing with CRC stage. High infiltration of GPNMB+ Macr was associated with poor prognosis in terms of overall and recurrence-free survival in CRC patients. GPNMB+ Macrophages exhibit M2-like characteristics and have the ability to promote 5-FU resistance, proliferation, and metastasis of CRC cells. The study developed the Hypoxia-Related Macrophage Risk Score (HMRS), which not only served as an independent prognostic factor for CRC patients but also demonstrated robust prognostic performance compared to 84 previously published prognostic features. Patients with low HMRS were sensitive to fluorouracil, oxaliplatin (FOLFOX), and anti-PD-1 immunotherapy, while those with high HMRS showed resistance. Additionally, HMRS was identified as an independent prognostic factor in other digestive tract tumors (hepatocellular carcinoma, pancreatic cancer, esophageal cancer, and gastric cancer), indicating potential extrapolation to other tumor types. In conclusion, GPNMB+ Macr promotes the malignant progression of CRC, and HMRS serves as a powerful predictive tool for prognosis, chemotherapy, and immunotherapy in CRC patients, aiding in improving the quality of survival.

Impact of web-based positive psychological intervention on emotions, psychological capital, and quality of life in gastric cancer patients on chemotherapy.

Gastric cancer is a malignant digestive tract tumor that originates from the epithelium of the gastric mucosa and occurs in the gastric antrum, particularly in the lower curvature of the stomach. To evaluate the impact of a positive web-based psychological intervention on emotions, psychological capital, and quality of survival in gastric cancer patients on chemotherapy. From January 2020 to October 2023, 121 cases of gastric cancer patients on chemotherapy admitted to our hospital were collected and divided into a control group (n = 60) and an observation group (n = 61) according to the admission order. They were given either conventional nursing care alone and conventional nursing care combined with web-based positive psychological interventions, respectively. The two groups were compared in terms of negative emotions, psychological capital, degree of cancer-caused fatigue, and quality of survival. After intervention, the number of patients in the observation group who had negative feelings toward chemotherapy treatment was significantly lower than that of the control group (P < 0.05); the Positive Psychological Capital Questionnaire score was considerably higher than that of the control group (P < 0.05); the degree of cancer-caused fatigue was significantly lower than that of the control group (P < 0.05); and the Quality of Life Scale for Cancer Patients (QLQ-30) score was significantly higher than that of the control group (P < 0.05). Implementing a web-based positive psychological intervention for gastric cancer chemotherapy patients can effectively improve negative emotions, enhance psychological capital, and improve the quality of survival.

TOB1 inhibits the gastric cancer progression by focal adhesion pathway and ERK pathway based on transcriptional and metabolic sequencing

Gastric cancer is one of the most malignant digestive tract tumors worldwide and its progression is associated with gene expression and metabolic alteration. We revealed that the gastric cancer patients with lower expression level of TOB1 exhibited poorer overall survivals according to the data in Kaplan–Meier Plotter. The unphosphorylated TOB1 protein which is effective expressed lower in gastric cancer cells. The gastric cancer cells with TOB1 gene depletion performed higher abilities of proliferation, migration and invasion and lower ability of apoptosis in vitro. The TOB1 gene depletion also promoted the tumorigenesis of gastric cancer cells in vivo. The gastric cancer cells with TOB1 gene overexpression had the converse behaviors. The transcriptional and metabolic sequencing was performed. The analyzation results showed that genes correlate-expressed with TOB1 gene were enriched in the pathways related to ERK pathway, including focal adhesion pathway, which was verified using real-time quantitative PCR. After inhibiting ERK pathway, the proliferation, colony formation and migration abilities were reduced in gastric cancer cells with low phosphorylated TOB1 protein expression level. Moreover, Pearson correlation analysis was adopted to further analyze the correlation of enriched metabolic products and differentially expressed genes. The expression of Choline, UDP-N-acetylglucosamine, Adenosine and GMP were related to the function of TOB1. This study demonstrates the genes and metabolites related to focal adhesion pathway and ERK pathway are the potential diagnosis and therapeutic targets to gastric cancer with TOB1 depletion.

Fructose-1, 6-Bisphosphate Aldolase B Suppresses Glycolysis and Tumor Progression of Gastric Cancer.

Gastric cancer (GC) is believed to be one of the most common digestive tract malignant tumors. However, mounting evidence indicates a link between the glycolysis and tumorigenesis, including gastric cancer. Our research identified 5508 differently expressed mRNAs in gastric cancer. Then, the genes highly associated with tumorigenesis were identified through weighted correlation network analysis (WGCNA). Bioinformatics analysis observed that these hub genes were significantly linked to the regulation of cell cycle, drug metabolism, and glycolysis. Among these hub genes, there is a critical gene involved in glycolysis regulation, namely fructose-bisphosphate B (ALDOB). Analysis based on The Cancer Genome Atlas (TCGA) and three Gene Expression Omnibus (GEO) datasets revealed that ALDOB was significantly downregulated in GC compared with normal tissues. In addition, cell viability assay confirmed that ALDOB acted as a tumor suppressor. Finally, drug sensitivity analysis revealed that ALDOB increased the sensitivity of gastric cancer cells to most antitumor drugs, especially talazoparib, XAV939, and FTI-277. Our results showed that the expression of ALDOB was significantly lower in GC tissues than in normal tissues. And ALDOB significantly inhibited proliferation and migration, delayed glycolysis in GC cells. Consequently, our study suggests that ALDOB may be a potential target for the clinical treatment of gastric cancer.

Application of 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging in recurrent anastomotic tumors after surgery in digestive tract tumors.

This study was to investigate the application value of whole-body dynamic 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging in recurrent anastomotic tumors of digestive tract after gastric and esophageal cancer surgery. Postoperative patients with gastric and esophageal cancer have a high risk of tumor recurrence, and traditional imaging methods have certain limitations in early detection of recurrent tumors. Whole-body dynamic 18F-FDG PET/CT imaging, due to its high sensitivity and specificity, can provide comprehensive information on tumor metabolic activity, which is expected to improve the early diagnosis rate of postoperative recurrent tumors, and provide an important reference for clinical treatment decision-making. To investigate the clinical value of whole-body dynamic 18F-FDG PET/CT imaging in differentiating anastomotic recurrence and inflammation after the operation of upper digestive tract tumors. A retrospective analysis was performed on 53 patients with upper digestive tract tumors after operation and systemic dynamic 18F-FDG PET/CT imaging indicating abnormal FDG uptake by anastomosis, including 29 cases of gastric cancer and 24 cases of esophageal cancer. According to the follow-up results of gastroscopy and other imaging examinations before and after PET/CT examination, the patients were divided into an anastomotic recurrence group and anastomotic inflammation group. Patlak multi-parameter analysis software was used to obtain the metabolic rate (MRFDG), volume of distribution maximum (DVmax) of anastomotic lesions, and MRmean and DVmean of normal liver tissue. The lesion/background ratio (LBR) was calculated by dividing the MRFDG and DVmax of the anastomotic lesion by the MRmean and DVmean of the normal liver tissue, respectively, to obtain LBR-MRFDG and LBR-DVmax. An independent sample t test was used for statistical analysis, and a receiver operating characteristic curve was used to analyze the differential diagnostic efficacy of each parameter for anastomotic recurrence and inflammation. The dynamic 18F-FDG PET/CT imaging parameters MRFDG, DVmax, LBR-MRFDG, and LBR-DVmax of postoperative anastomotic lesions in gastric cancer and esophageal cancer showed statistically significant differences between the recurrence group and the inflammatory group (P < 0.05). The parameter LBR-MRFDG showed good diagnostic efficacy in differentiating anastomotic inflammation from recurrent lesions. In the gastric cancer group, the area under the curve (AUC) value was 0.935 (0.778, 0.993) when the threshold was 1.83, and in the esophageal cancer group, the AUC value was 1. When 86 is the threshold, the AUC value is 0.927 (0.743, 0.993). Whole-body dynamic 18F-FDG PET/CT imaging can accurately differentiate the diagnosis of postoperative anastomotic recurrence and inflammation of gastric cancer and esophageal cancer and has the potential to be an effective monitoring method for patients with upper digestive tract tumors after surgical treatment.

Identification of candidate biomarkers and prognostic analysis of recurrence in colorectal cancer.

Colorectal cancer (CRC) is one of the most common digestive tract malignant tumors, which has a high mortality rate especially for patients with CRC recurrence. However, the pathological mechanism of recurrence of CRC is unclear. In this study, we integrated multiple cohort datasets and databases to clarify and verify potential key candidate biomarkers and signal transduction pathways in recurrence of CRC. As results, 628 DEGs were identified from GSE33113 and GSE2630 datasets and their function and pathway were analyzed. 14 hub genes related to CRC recurrence were screened from and their influence on survival were analyzed. Two key genes (IL1B and DDAH1) regarded as prognostic factors were further screened. Relapse-free survival results indicated the interaction between IL1B and DDAH1 genes and B cells was the most obvious and correlated with survival, with statistical significance (P< 0.05). Specially, cox regression analysis suggested that patients with T1 and N0 stages had a higher risk of recurrence than patients with T2 and N1. This work would provide potential value for prognosis, and would promote molecular targeting therapy for CRC recurrence.

Identification of Clinical Value and Biological Effects of XIRP2 Mutation in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent malignant digestive tumor. Numerous genetic mutations have been documented in HCC, yet the clinical significance of these mutations remains largely unexplored. The objective of this study is to ascertain the clinical value and biological effects of xin actin binding repeat containing 2 (XIRP2) mutation in HCC. The gene mutation landscape of HCC was examined using data from the Cancer Genome Atlas and the International Cancer Genome Consortium databases. The prognostic significance of the XIRP2 mutation was assessed through KM plot analysis. The association between drug sensitivity and the XIRP2 mutation was investigated using the TIDE algorithm and CCK-8 experiments. The biological effects of the XIRP2 mutation were evaluated through qRT-PCR, protein stability experiments, and relevant biological experiments. The XIRP2 mutation is one of the high-frequency mutations in HCC, and is associated with poor prognosis. A total of 72 differentially expressed genes (DEGs) were observed in HCC tissues with the XIRP2 mutation as compared to those with the XIRP2 wildtype, and these DEGs were closely related to ion metabolic processes. The XIRP2 mutation was linked to alterations in the sensitivity of fludarabine, oxaliplatin, WEHI-539, and LCL-161. CCK-8 assays demonstrated that HCC cells carrying the XIRP2 mutation exhibited increased resistance to fludarabine and oxaliplatin, but enhanced sensitivity to WEHI-539 and LCL-161 as compared with those HCC cells with the XIRP2 wildtype. The XIRP2 mutation was found to have no impact on the mRNA levels of XIRP2 in tissues and cells, but it did enhance the stability of the XIRP2 protein. Mechanically, the inhibition of XIRP2 resulted in a significant increase in sensitivity to oxaliplatin through an elevation in zinc ions and a calcium ion overload. In conclusion, the XIRP2 mutation holds potential as a biomarker for predicting the prognosis and drug sensitivity of HCC and serves as a therapeutic target to enhance the efficacy of oxaliplatin.

Applicability of Global Leadership Initiative on Malnutrition (GLIM) criteria in nutrition risk screening for patients over 60 years old with digestive system tumors – A retrospective study

ObjectiveThis study aimed to identify the most effective nutritional risk screening tool for elderly patients with digestive system tumors. MethodsNutritional risk screening was performed using Nutritional Risk Screening 2002 (NRS2002), prognostic nutritional index (PNI) and Geriatric Nutritional Risk Index (GNRI) for elderly patients who underwent surgical resection of digestive tumor. Comparative analysis of each nutritional screening tool was conducted through Kappa test and ROC curve. ResultsMalnourished individuals diagnosed by the Global Leadership Initiative on Malnutrition (GLIM) criteria had lower levels of hematological parameters (serum albumin, pre-albumin, total protein and hemoglobin) and poorer body composition parameters (body mass index, body fat percentage, edema index, upper arm muscle circumference, skeletal muscle index, and phase angle; P<0.05). NRS2002 demonstrated a sensitivity of 75.56% and specificity of 38.16% under the GLIM criteria, showing moderate agreement (Kappa=0.346, P<0.001). PNI had an average sensitivity of 71.11% and the highest specificity at 87.23%, but exhibited no consistency with GLIM (Kappa=0.152, P=0.062). GNRI showed the highest sensitivity at 91.11% and general specificity at 37.14%, aligning closely with GLIM criteria (Kappa=0.711, P<0.001). GNRI had the highest predictive value (AUC=0.870, 95% CI: 0.801–0.939), followed by NRS2002 (AUC=0.687, 95% CI: 0.589–0.785). Patients diagnosed with malnutrition via GNRI-GLIM exhibited higher rates of surgical site infection (χ2=15.534, P<0.001) and 3-month readmission (χ2=4.499, P=0.034). ConclusionGNRI and NRS2002 demonstrate good performance as GLIM criteria for nutritional screening in elderly patients with digestive tumors, with GNRI being potentially more suitable. Moreover, GNRI-GLIM can predict short-term prognosis in these patients.

A comprehensive prognostic and immune infiltration analysis of UBA1 in pan-cancer: A computational analysis and invitro experiments.

Ubiquitin like modifier activating enzyme 1 (UBA1) plays an important role in immune regulation and cellular function. However, the functional mechanism and role of UBA1 in pan-cancer have not been fully elucidated and its value in haematological tumours (diffuse large B cell lymphoma (DLBC/DLBCL) and acute myeloid leukaemia (AML/LAML)) has not been explored. We conducted a comprehensive analysis of the functional mechanism and role of UBA1 in pan-cancer using multiple databases, including differential expression analysis, clinical pathological staging analysis, prognosis analysis and immune analysis. Then, we confirmed the function of UBA1 in haematological tumours through cell experiments. The results showed that the expression of UBA1 was significantly increased in most cancers and the differential expression of UBA1 was mainly concentrated in digestive tumours, haematological tumours and brain tumours. Moreover, the high expression of UBA1 had poor prognosis in most tumours, which may be related to its involvement in various cancer-related pathways such as cell cycle, as well as its methylation level, protein phosphorylation level, immune cell infiltration and immune therapy response. Cell experiments have confirmed that UBA1 can significantly regulate the cycle progression and apoptosis of DLBCL cells and AML cells. Therefore, UBA1 may be a potential therapeutic target for haematological tumours. In summary, our study not only comprehensively analysed the functional mechanisms and clinical value of UBA1 in pan-cancer, but also validated for the first time the regulatory role of UBA1 in haematological tumours.

Soluble Tim-3 serves as a tumor prognostic marker and therapeutic target for CD8+ T cell exhaustion and anti-PD-1 resistance

Resistance to PD-1 blockade in onco-immunotherapy greatly limits its clinical application. Tcell immunoglobulin and mucin domain containing-3 (Tim-3), a promising immune checkpoint target, is cleaved by ADAM10/17 to produce its soluble form (sTim-3) in humans, potentially becoming involved in anti-PD-1 resistance. Herein, serum sTim-3 upregulation was observed in non-small cell lung cancer (NSCLC) and various digestive tumors. Notably, serum sTim-3 is further upregulated in non-responding patients undergoing anti-PD-1 therapy for NSCLC and anti-PD-1-resistant cholangiocarcinoma patients. Furthermore, sTim-3 overexpression facilitates tumor progression and confers anti-PD-1 resistance in multiple tumor mouse models. Mechanistically, sTim-3 induces terminal Tcell exhaustion and attenuates CD8+ Tcell response to PD-1 blockade through carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1). Moreover, the ADAM10 inhibitor GI254023X, which blocks sTim-3 production, reduces tumor progression in Tim-3 humanized mice and reverses anti-PD-1 resistance in human tumor-infiltrating lymphocytes (TILs). Overall, human sTim-3 holds great predictive and therapeutic potential in onco-immunotherapy.

Intelligent treatment system based on bioinformatics and neuro-immune-digestive tract diseases

There are currently many clinical issues plaguing digestive oncologists, including the impact of dietary habits on the occurrence of early gastrointestinal cancer, the association between irritable bowel syndrome, ulcerative colitis, and early gastrointestinal cancer, the expected changes in gastrointestinal cancer after IBS, IBD, and susceptibility gene mutations, and the mechanisms by which susceptibility gene mutations in gastrointestinal cancer lead to different diseases. Meanwhile, as a carcinogen, betel nut is also prone to cancer and emotional disorders, and there are also many doctor-patient conflicts in the current clinical treatment of digestive tract tumors. To address the aforementioned issues, the research team analyzed dietary habits data using SOM clustering algorithm and isolated forest algorithm. Based on bioinformatics, new therapies have been developed for the pathogenesis and immune pathways of various cancers in the digestive system. Using network pharmacology methods, explore the toxicological mechanism of betel nut and its mechanism in mediating emotional disorders. Molecular docking is used to elucidate drug prediction. Based on four AI algorithms, the occurrence of gastrointestinal cancer was predicted through dietary habits. Using computer vision technology to address the deficiencies in early clinical reporting of cancer. This article provides clinical doctors with new treatment tools.

The Role and Function of TRPM8 in the Digestive System.

Transient receptor potential (TRP) melastatin member 8 (TRPM8) is a non-selective cation channel that can be activated by low temperatures (8-26 °C), cooling agents (including menthol analogs such as menthol, icilin, and WS-12), voltage, and extracellular osmotic pressure changes. TRPM8 expression has been identified in the digestive system by several research teams, demonstrating its significant involvement in tissue function and pathologies of the digestive system. Specifically, studies have implicated TRPM8 in various physiological and pathological processes of the esophagus, stomach, colorectal region, liver, and pancreas. This paper aims to comprehensively outline the distinct role of TRPM8 in different organs of the digestive system, offering insights for future mechanistic investigations of TRPM8. Additionally, it presents potential therapeutic targets for treating conditions such as digestive tract inflammation, tumors, sensory and functional disorders, and other related diseases. Furthermore, this paper addresses the limitations of existing studies and highlights the research prospects associated with TRPM8.

Neutrophil extracellular traps-related lncRNAs prognostic signature for gastric cancer and immune infiltration: potential biomarkers for predicting overall survival and clinical therapy

Gastric cancer (GC) is one of the most common digestive tract malignant tumors in the world. At the time of initial diagnosis, it frequently presents with local or distant metastasis, contributing to poor prognosis in patients. Neutrophil extracellular traps (NETs) constitute a mechanism employed by neutrophils that is intricately associated with tumor progression, prognosis, and response to immunotherapy and chemotherapy. Despite this, the specific involvement of NETs-related long non-coding RNAs (lncRNAs) in gastric cancer remains unclear. A prognostic model for NETs-related lncRNAs was constructed through correlation analysis, COX regression analysis, and least absolute shrinkage and selection operator regression (LASSO) analysis. The predictive performance of the model was assessed using Kaplan–Meier survival curves, receiver operating characteristic (ROC) curves, facilitating the exploration of the relationship between disease onset and prognosis in gastric cancer. Additionally, differences in the tumor microenvironment and response to immunotherapy among gastric cancer patients across high- and low-risk groups were analyzed. Furthermore, a prognostic nomogram integrating the risk score with relevant clinicopathological parameters was developed. The prognostic prediction model for gastric cancer, derived from NETs-related lncRNAs in this study, demonstrates robust prognostic capabilities, serving as a valuable adjunct to traditional tumor staging. This model holds promise in offering novel guidelines for the precise treatment of gastric cancer, thereby potentially improving patient outcomes.

Analysis of sleep quality, disease uncertainty, and psychological tolerance in patients undergoing chemotherapy for digestive tract malignancies.

Colorectal cancer is the second leading cause of cancer-related deaths among digestive tract malignancies, following gastric cancer. Sleep is of great significance for maintaining human health. The incidence of sleep disorders in patients with cancer is approximately twice that observed in the general population. Lack of sleep can prolong hospital stays, increase the likelihood of infection, and increase mortality rates. Therefore, studying the factors related to sleep quality is significant for improving the quality of life of patients with malignant tumors of the digestive tract. To investigate the relationships among sleep quality, disease uncertainty, and psychological resilience in patients undergoing chemotherapy for digestive tract malignancies. A total of 131 patients with malignant digestive tract tumors who were treated at Hefei BOE Hospital between April 2021 and September 2022 were selected as research participants. Based on their Pittsburgh Sleep Quality Index (PSQI) scores, participants were divided into either the sleep disorder group (PSQI score > 7) or the normal sleep group (PSQI score ≤ 7). The clinical data-together with the Mishel Uncertainty in Illness Scale for Adults (MUIS-A) and Connor-Davidson Resilience Scale (CD-RISC) scores-were compared. In this study, 78 (59.54%) patients with digestive tract malignancies developed sleep disorders after chemotherapy. Sleep disorder incidence was higher in patients with colorectal cancer than in those with gastric and esophageal cancers (P < 0.05). The total MUIS-A score and those for each item in the sleep disorder group were higher than those in the normal sleep group. The total CD-RISC score and those for each item in the sleep disorder group were lower than those in the normal sleep group (P < 0.05). The PSQI scores of patients with malignant digestive tract tumors were positively correlated with the scores for lack of disease information, disease uncertainty, and unpredictability in the MUIS-A and negatively correlated with the scores for tenacity, self-improvement, and optimism in the CD-RISC (P < 0.05). Patients undergoing chemotherapy for digestive tract malignancies are prone to sleep problems related to disease uncertainty and psychological resilience. Therefore, interventions can be implemented to improve their sleep quality.